Despite other TKIs have been approved for frontline CML treatment,
imatinib (IM) is an important therapeutic option. Response criteria at
given time points have been proposed by the ELN panel, irrespectively
of the first-line TKI used, to decide when the treatment should be continued,
optimal response (OR), or changed, failure (F); warning (W) is an
intermediate zone. To investigate the significance of 2013 ELN response
criteria in CML treated frontline with IM, 559 patients enrolled within
3 prospective studies (CML021-022-023) were analyzed (ITT population
of each study). ELN criteria at 3 months: not fully evaluable due to missing
cytogenetic analysis in 452/559 patients; we focused on the early
molecular response (EMR, BCR-ABL <10% at 3 months, corresponding
to OR). ELN criteria at 6 and 12 months: F, BCR-ABL >10% and/or Ph+
>35% at 6 months, BCR-ABL >1% and/or Ph+ >0 at 12 months; OR,
BCR-ABL <1% and/or Ph+ 0 at 6 months, BCR-ABL <0.1% at 12
months; W: intermediate conditions. Progression: according to 2013 ELN
criteria. Molecular response: according to 2015 EUTOS recommendations.
Leukemia-unrelated death (LRD): known cause of death, no progression,
CCyR or MMR <6 months prior to death; all other deaths were
classified as leukemia-related. Median follow-up, 76 (66-99) months.
The EMR rate was 82%. The progression-free survival (PFS) and the
probability of LRD according to the presence-absence of EMR were
91%-87% (p=0.035) and 11%-5% (p=0.019), respectively. Combining
Sokal score and EMR, the patients were divided into 4 groups, LR-IR
resp, LR-IR not resp, HR resp, HR not resp: the probability of LRD was
3%-9%-10%-20% (p<0.001). The patients remaining on IM according
to the response at 6 months (OR-W-F) were 77%-52%-26%, respectively.
The PFS and the probability of LRD according to ELN response
at 6 months (OR-W-F) were 93%-92%-77% (p<0.001) and 2%-5%-28%
(p<0.001), respectively. The patients remaining on IM according to the
response at 12 months (OR-W-F) were 80%-72%-35%, respectively.
The PFS and the probability of LRD according to ELN response criteria
at 12 months (OR-W-F) were 95%-96%-85% (p<0.001) and 1%-1%-
16% (p<0.001), respectively. Patients without OR at 3 months (particularly
high risk patients) had poorer outcome compared to patients with
OR. Patients classified as W at 6 and 12 months have similar outcome
to OR patients, both significantly better than F. The subsequent treatment
may explain, at least in part, the absence of differences.